Tetrahydrofuran → HCID 22462739, compound

HRID 1937171Notes

Reaction equation

HRID 1937171 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH:27]([Si:30]([CH:50]([CH3:52])[CH3:51])([CH:47]([CH3:49])[CH3:48])[O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:42][C:41]3[CH:43]=[CH:44][CH:45]=[CH:46][C:40]=3[CH:39]=2)=[CH:34][CH:33]=1)([CH3:29])[CH3:28].C1COCC1>ClC(Cl)C.CN(C=O)C.Cl[Ti](Cl)(Cl)Cl>[CH:50]([Si:30]([CH:27]([CH3:29])[CH3:28])([CH:47]([CH3:49])[CH3:48])[O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:42][C:41]3[CH:43]=[CH:44][CH:45]=[CH:46][C:40]=3[C:39]=2[C:7]([C:6]2[CH:10]=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[C:4]([O:3][CH3:2])[CH:5]=2)=[O:9])=[CH:34][CH:33]=1)([CH3:52])[CH3:51]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 15550250HCID 15550250, compoundHCID 69690284HCID 69690284, compound

Product 1

HCID 22462739HCID 22462739, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 24193Titanium TetrachlorideCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A slurry of 4.34 g (14.4 mmol) of 3-methoxy-4-[2-(1-pyrrolidinyl)ethoxy]benzoic acid hydrochloride (Part G, below) in 75 mL of dichloroethane was treated with 2 drops of DMF followed by 5.00 mL (57.3 mmol; 4 eq) of oxalyl chloride. The reaction was stirred at ambient temperature until gas evolution ceased and was concentrated in vacuo. The solid was reconstituted in 75 mL dichloroethane. The mixture was cooled to 0° C., treated with 5.00 g (13.0 mmol; 0.9 eq) of 2-(4-triisopropylsilyloxyphenyl)benzo[b]thiophene (Part B) and 6.40 mL (58.4 mmol; 4 eq) of TiCl4, and stirred at ambient temperature for 5 h. The reaction was quenched by the addition of 50 mL of sat'd aq NaHCO3. The two layers were separated and the aqueous layer was extracted with EtOAc (4×25 mL). The combined organic layers were washed with H2O (50 mL), dried over K2CO3, filtered, and concentrated in vacuo to give an oil. Flash chromatography (SiO2; 15% THF and 5% TEA in hexanes) afforded 5.60 g (8.90 mmol; 62%) of the title compound as an oil.

Workup

  1. concentrationwas concentrated in vacuo
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringstirred at ambient temperature for 5 h
  4. customThe reaction was quenched by the addition of 50 mL of sat'd aq NaHCO3
  5. customThe two layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (4×25 mL)
  7. washThe combined organic layers were washed with H2O (50 mL)
  8. dry with materialdried over K2CO3
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give an oil

Sources & evidence

ORD record
ord-e2bdc0b53e8b40d3ac09bcd537053fcc
Source dataset
uspto-grants-2002_05
Patent number
US06391901B1

Reaction notes

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